Endocrine Abstracts

Patients with glucocorticoid excess develop a phenotype characterized by central obesity, however, the impact of glucocorticoids upon the processes that regulate lipid accumulation has not been fully explored. We hypothesize that intracellular generation of cortisol from cortisone by 11b-hydroxysteroid dehydrogenase type 1 (11bHSD1) is an important regulator of lipid metabolism.In adipocytes, acetyl-CoA carboxylase 1 and 2 (ACC1/2) convert acetyl-CoA to ...

The eye is an organ vulnerable to a variety of external and internal stimuli that can abolish its vital function to allow accurate vision of images for survival. Inflammation is the key mediator of immune protection but its consequence leads to the disruption of the visual axis integrity. Due to this precise reason, through adaptation and evolution, the eye has developed mechanisms of immune tolerance and privilege. Glucocorticoids have potent immunosuppressive and anti-inflam...

Hexose-6-phosphate dehydrogenase (H6PD) is a sarcoplasmic reticulum (SR) resident enzyme that metabolizes glucose-6-phosphate and generates NADPH that drives the activation of glucocorticoids by 11β-hydroxysteorid dehydrogenase type 1. H6PD KO mice exhibit improved skeletal muscle insulin sensitivity increased glucose uptake and glycogen storage. However, H6PD KO mice also develop a myopathy with switching from Type II to Type I fibers. Affected muscles have apparently no...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin GC mediated changes in insulin signalling are not clear. Within skeletal muscle, the microsomal enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GC, 11-dehydrocorticosterone (A) to active corticosterone (B) and thus regulates GC availabi...

In humans, glucocorticoids (GC) are implicated in the pathogenesis of obesity and insulin resistance. In adipose tissue, GCs are regulated at the prereceptor level by oxo-reductase activity of 11beta-hydroxysteroid dehydrogenases type 1 (11β-HSD1). The hexose-6-phosphate dehydrogenase null mouse (H6PDH/KO) has shown that H6PDH is required for generating NADPH within the endoplasmic reticulum which determines the direction of 11β-HSD1 enzyme. We have shown that mRNA f...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin the GC mediated changes in insulin signalling are not clear. The majority of previous studies have used rodent models and have shown regulation at the level of the insulin receptor (IR), IRS-1 and PI3 kinase.Primary cultures of human skeletal myocytes ...

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...

In humans, glucocorticoids (GC) are implicated in the pathogenesis of obesity and insulin resistance. GCs are regulated at the prereceptor level by 11beta-HSDs. 11beta-HSD1 predominately displays oxo-reductase activity (cortisone/11-dehydrocorticosterone to cortisol/ corticosterone), requiring the cofactor NADPH. Recently, studies in humans have shown that the enzyme H6PDH, by generating NAPDH in the endoplasmic reticulum (ER) is crucial for oxo-reductase activity. This study ...

Glucocorticoids (GCs) are important therapeutic agents for a wide-variety of inflammatory diseases but are known to have potentially detrimental side-effects such as osteoporotic bone-loss. These effects of GCs are mediated via the intracellular GC receptor (GR) and by local GC metabolism catalyzed by 11beta-hydroxysteroid dehydrogenase (11beta-HSD). We have postulated that autocrine activation of GCs via 11beta-HSD1 plays a key role in counteracting the effects of inflammator...

Studies in rats suggest that androgens are involved in sex-specific differences in blood pressure. In human studies there is no difference in blood pressure between boys and girls, but following puberty, men present with a higher blood pressure than women. Modulation of sodium reabsorption through the ENaC is an important component in the control of sodium balance. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohy...